Cerebral palsy and its medicolegal implications in low- resource settings - the need to establish causality and revise criteria to implicate intrapartum hypoxia: A narrative review.

The objective of this study was to establish scientific causality and to devise criteria to implicate intrapartum hypoxia in cerebral palsy (CP) in low-resource settings, where there is potential for an increase in damaging medicolegal claims against obstetric caregivers, as is currently the situation in South Africa. For the purposes of this narrative review, an extensive literature search was performed, including any research articles, randomised controlled trials, observational studies, case reports or expert or consensus statements pertaining to CP in low-resource settings, medicolegal implications, causality, and criteria implicating intrapartum hypoxia. In terms of causation, there are differences between high-income countries (HICs) and low-resource settings. While intrapartum hypoxia accounts for 10 - 14% of CP in HICs, the figure is higher in low-resource settings (20 - 46%), indicating a need for improved intrapartum care. Criteria implicating intrapartum hypoxia presented for HICs may not apply to low-resource settings, as cord blood pH testing, neonatal brain magnetic resonance imaging (MRI) and placental histology are frequently not available, compounded by incomplete clinical notes and missing cardiotocography tracings. Revised criteria in an algorithm for low-resource settings to implicate intrapartum hypoxia in neonatal encephalopathy (NE)/ CP are presented. The algorithm relies first on specialist neurological assessment of the child, determination of the occurrence of neonatal encephalopathy (by documented or verbal accounts) and findings on childhood MRI, and second on evidence of antepartum and intrapartum contributors to the apparent hypoxia-related CP. The review explores differences between low-resource settings and HICs in trying to establish causation in NE/CP and presents a revised scientific approach to causality in the context of low-resource settings for reaching appropriate legal judgments.

Clinical practice.

Basal ganglia and thalamus (BGT) hypoxic-ischaemic brain injury is currently the most contentious issue in cerebral palsy (CP) litigation in South Africa (SA), and merits a consensus response based on the current available international literature. BGT pattern injury is strongly associated with a preceding perinatal sentinel event (PSE), which has a sudden onset and is typically unforeseen and unpreventable. Antepartum pathologies may result in fetal priming, leading to vulnerability to BGT injury by relatively mild hypoxic insults. BGT injury may uncommonly follow a gradual-onset fetal heart rate deterioration pattern, of duration ≥1 hour. To prevent BGT injury in a clinical setting, the interval from onset of PSE to delivery must be short, as little as 10 - 20 minutes. This is difficult to achieve in any circumstances in SA. Each case needs holistic, multidisciplinary, unbiased review of all available antepartum, intrapartum and postpartum and childhood information, aiming at fair resolution without waste of time and resources.

Trisomy 21 screening with αlpha software and the Fetal Medicine Foundation algorithm.

BACKGROUND: Screening for trisomy 21 provides pregnant women with accurate risk information. Different algorithms are used to screen for trisomy 21 in South Africa (SA). The Fetal Medicine Foundation (FMF) provides software to screen for trisomy 21 in the first trimester by ultrasound or a combination of ultrasound and biochemistry (combined screening), and requires regular and stringent quality control. With αlpha software, first trimester combined screening and screening with biochemistry alone in the first or second trimester are possible. The αlpha screening requires quality control of biochemical tests, but not of ultrasound measurements. Ideally, a screening test should have a high detection and a low screen positive rate. Despite the availability of these screening programmes, only a minority of infants with trisomy 21 are detected prenatally, raising questions about the effectiveness of screening. OBJECTIVES: To determine the screen positive and detection rates of prenatal screening for trisomy 21 in the SA private healthcare system. METHODS: Data from the three largest laboratories collected between 2010 and 2015 were linked with genetic tests to assess screen positive and detection rates. Biochemical screening alone with αlpha software (first or second trimester) and combined screening using either FMF or αlpha software were compared. RESULTS: One-third of an estimated 675 000 pregnancies in private practice in the 6-year study period underwent screening. There were 687 cases of trisomy 21 in 225 021 pregnancies, with only 239 (35%) diagnosed prenatally. The screen positive rates were 11.8% for first trimester biochemistry, 7.6% for second trimester biochemistry, 7.3% for first trimester FMF software ultrasound alone, 3.7% for combined first trimester screening with FMF software, and 3.5% for combined first trimester screening with αlpha software. The detection rates for a 5% false positive rate were 63% for first trimester biochemistry, 69% for second trimester biochemistry, 95% for combined first trimester screening with FMF software and 80% for combined first trimester screening with αlpha software. Detection and confirmation rates were highest with FMF software. CONCLUSION: Screening with FMF software has a similar screen positive rate and better detection rate than screening with αlpha software. The low prenatal detection rate of trisomy 21 is mainly due to a low prevalence of screening. More research is needed in the SA setting to explore why screening and confirmatory testing after high-risk results are not performed in many pregnancies.

Right of Reply.

To the Editor: The article by Bhorat et al. [1] in the SAMJ, entitled 'Cerebral palsy and criteria implicating intrapartum hypoxia in neonatal encephalopathy - an obstetric perspective for the South African setting', starts off by raising concerns about 'steep rises in insurance premiums, placing service delivery under serious threat'. It does not acknowledge any service delivery issues that already exist in the public sector obstetric services in South Africa (SA). According to Whittaker,[2] in 2019, there were 303 obstetricians and gynaecologists employed in the SA public sector and 579 in the private sector, and of those employed in the public sector, 190 were performing private sector work. That a large number of the children with cerebral palsy (CP) were delivered in the public sector service was not noted by Bhorat et al.,[1] nor was the fact that the overwhelming majority of court cases are against the state (not against individual doctors) in provinces and hospitals with significant medical staffing and resource issues. For example, the liabilities for Eastern Cape Province in the 2019/20 period were ZAR36 751 207 v. only ZAR33 155 in Western Cape Province for the same period.[2].

Cerebral Palsy and Criteria Implicating Intrapartum Hypoxia in Neonatal Encephalopathy - An Obstetric Perspective for the South African Setting.

The science surrounding cerebral palsy indicates  that it is a complex medical condition with multiple contributing variables and factors, and causal pathways are often extremely difficult to delineate. The pathophysiological processes are often juxtaposed on antenatal factors, genetics, toxins, fetal priming, failure of neuroscientific autoregulatory mechanisms, abnormal biochemistry and abnormal metabolic pathways. Placing this primed compromised compensated brain through the stresses of an intrapartum process could be the final straw in the pathway  to brain injury and later CP.  It is thus simplistic to base causation of cerebral palsy on only an intrapartum perspective with radiological 'confirmation', as is often the practice in medicolegal cases in South African courts. The present modalities (MRI and CTG when available) that retrospectively attempt to determine causation in courts are inadequate when used in isolation. Unless a holistic scientific review of the case including all contributing clinical factors (antepartum, intrapartum and neonatal), fetal heart rate monitoring, neonatal MRI if possible (and preferred) or late MRI, and histology (placental histology if performed) are taken into account, success for plaintiff or defendant currently in a court of law will depend on eloquent legal argument rather than true scientific causality. The 10 criteria set out in this document to implicate acute intrapartum hypoxia in hypoxic ischaemic encephalopathy/neonatal encephalopathy serve as a guideline in the medicolegal setting.

The clinical prognostic significance of myocardial performance index (MPI) in stable placental-mediated disease.

AIM: To determine whether a single elevated myocardial performance index (MPI) value in the third trimester of pregnancy is a marker for later adverse obstetric outcomes in stable placental-mediated disease, defined as well-controlled pre-eclampsia (PE) on a single agent and/or uncompensated intra-uterine growth restriction (IUGR). METHODS: Fifty-five foetuses whose mothers had stable placental-mediated disease, either mild pre-eclampsia controlled on a single agent, and/or uncompensated IUGR in the third trimester, attending the Foetal Unit at Inkosi Albert Luthuli Hospital, Durban, South Africa were prospectively recruited with 55 matched controls. Recorded data for the subjects included demographic data of maternal age and parity, sonographic data of estimated foetal weight (EFW) and amniotic fluid index (AFI), myocardial performance index (MPI), and foetal Doppler data of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV). RESULTS: The mean gestational age in the controls, the IUGR and any PE cases was 31.4, 31.8 and 31.0 weeks, respectively. The distribution of MPI values was significantly lower in the controls compared to all other groups. The highest standardised MPI values were observed in the PE-IUGR group, where a median of 5.62 was observed. The only significant differences observed between the PE and IUGR groups was the UA resistance index (p = 0.01), where the IUGR cases tended to have higher UA values compared to the combined PE group. Borderline statistical significance was observed for the MCA resistance index values ( p = 0.05) between these groups. The overall adverse event rate in the cases was 49%. The highest rate was observed in the PE + IUGR group, where eight out of 12 (67%) experienced adverse events. MPI z-scores served as a good marker of adverse events, as evidenced by the total area under the curve (AUC) of 0.90 on the ROC curve. A cut-off value of 4.5 on the MPI z-score conferred a sensitivity of 89% and specificity of 68% for an adverse event later in pregnancy. In univariate logistic regression, MPI z-score, AFI, EFW, UA Doppler, CPR category, DV Doppler and MCA Doppler were assessed separately as potential predictors of adverse outcome. The only significant predictor of adverse outcome was MPI z-score. CONCLUSIONS: A single elevated value of the MPI ( z-score > 4.5) in the third trimester in stable placental-mediated disease was a strong indicator of adverse obstetric outcomes later in pregnancy. This has the potential to be incorporated in conjunction with standard monitoring models in stable placental-mediated disease to predict an adverse event later in pregnancy and thus to reduce perinatal morbidity and mortality.

Assessment of fetal myocardial performance in severe early onset pre-eclampsia (EO-PET) with and without intrauterine growth restriction across deteriorating stages of placental vascular resistance and links to adverse outcomes.

OBJECTIVE: To determine whether fetuses in severe early onset pre-eclampsia (EO-PET) with or without intrauterine growth restriction has cardiac dysfunction across deteriorating stages of placental vascular resistance and whether this dysfunction influences perinatal outcome. STUDY DESIGN: This was a prospective cross-sectional study performed in a tertiary care university medical centre. Sixty pregnant patients with severe early-onset pre-eclampsia between 27 and 32 weeks were recruited and matched with 60 patients having normal pregnancies. An analysis of cardiac function using the myocardial performance index (MPI) and early ventricular filling (E) and late active atrial contraction (A) ratios (E/A ratios) in the study group was performed compared to controls and further analysis was performed based on worsening placental vascular resistance and presence of growth restriction. RESULTS: MPI values were increased in the pre-eclamptic group, irrespective if growth restriction co-exists, compared to controls (0.61 vs 0.38, p<0.001). Its median value progressively increased with worsening placental vascular resistance. For adverse perinatal outcome cut-off MPI values have been suggested. The E/A ratios were significantly decreased in the pre-eclamptic group compared to controls (0.66 vs 0.79, p<0.0001). No adverse outcomes were noted in the control group. CONCLUSION: Fetal cardiac function is significantly impaired in pregnancies complicated by severe early onset pre-eclampsia, irrespective if growth restriction co-exists and worsens with deteriorating grades of placental vascular resistance. The MPI can potentially be integrated into routine fetal surveillance techniques.

Maternal cardiac haemodynamics in severe pre-eclampsia complicated by acute pulmonary oedema: A review.

AIM: To establish alterations in maternal cardiac haemodynamics and function using electrocardiography and echocardiography in severe pre-eclampsia complicated by acute pulmonary oedema. METHODS: An extensive literature search including any research articles, randomised control trials, observational study, case report or expert or consensus statement pertaining to severe pre-eclampsia, eclampsia, hypertensive crises of pregnancy, pulmonary oedema, maternal cardiac haemodynamics, Holter monitoring and maternal echocardiography was done. Electronic search strategies included searching the MEDLINE, EMBASE, Cochrane Library and Pubmed databases. RESULTS: Toxic substrates from a chronically ischaemic placenta and elevated maternal cathecolamines leads to widespread elevated systemic vascular resistance, endothelial cell damage and increased left ventricular afterload all of which combine to result in left ventricular hypertrophy with impaired ventricular filling reflected as significant diastolic dysfunction, increased left ventricular end systolic and end diastolic volumes, increased left ventricular stroke work, myocardial ischaemia and resultant ventricular arrhythmias, in particular ventricular tachycardia. These factors could lead to cardiac failure in severe pre-eclampsia, either in combination or in independently of each other depending on the magnitude of the angiogenic imbalances, degree of elevated systemic vascular resistance, degree of impaired myocardial relaxation and diastolic filling anomalies, gene-environment interaction and degree of possible pre-existing or potential cardiovascular dysfunction. CONCLUSION: Comprehensive maternal echocardiographic and electocardiographic assessment should be incorporated in the work-up of severe pre-eclampsia to stratify these cases, to enable clinicians to choose the appropriate acute hypertensive drug therapy and plan optimal management pathways.

Determination of the myocardial performance index in deteriorating grades of intrauterine growth restriction and its link to adverse outcomes.

AIM: The aim of this study is to determine the fetal modified myocardial performance index (Mod-MPI) and E-wave/A-wave peak velocities (E/A ratio) in deteriorating grades of intrauterine growth restriction (IUGR) and its link to adverse outcomes defined as perinatal death, hypoxic ischemic encephalopathy, neonatal resuscitation, neonatal cord pH <7.15, intraventricular hemorrhage and bronchopulmonary dysplasia. METHOD: Forty three pregnant women with IUGR defined as the abdominal circumference <10th percentile for gestational age and umbilical resistance index >2 standard deviations in the third trimester of pregnancy were matched for gestational age and maternal age with 43 women with appropriate-for-gestational-age fetuses. The IUGR group was subdivided on the basis of multivessel Doppler anomalies into different grades of growth restriction. Mod-MPI and E/A ratio were determined and linked to perinatal outcome. RESULTS: The median Mod-MPI was significantly higher in growth-restricted fetuses compared with controls (0.59 vs 0.37, p < 0.001) and increased with severity of IUGR, the classification of which was based on degree of abnormality of the umbilical resistance index, presence of arterial redistribution and degree of abnormality of the ductus venosus (DV) Doppler indices. A cut-off Mod-MPI value of 0.54 conferred a sensitivity of 87% [confidence interval (CI): 66-97%], specificity of 75% (CI: 55-91%) and a likelihood ratio (LR) of 3.47 for an adverse outcome. A cut-off Mod-MPI value of 0.67 conferred a sensitivity of 100% (CI: 54-100%), specificity of 81% (CI: 65-92%) and LR of 5.28 for perinatal death. No abnormal outcomes occurred in controls. In logistic regression analysis, the MPI remained a significant predictor of adverse outcome after adjusting for gestational age of delivery, fetal weight, E/A ratio, maternal age, DV Doppler indices, amniotic fluid index and umbilical artery resistance index [adjusted odds ratio, 95% CI: 2.60 (1.15-5.83), p-value 0.02]. MPI fared significantly better than the E/A ratio as a predictor of adverse outcome (area under the receiver operating characteristic curve of 0.94 and 0.76, p < 0.001). CONCLUSION: Fetal myocardial performance deteriorates with severity of growth restriction. There is an association between severity of the MPI elevation and rates of adverse perinatal outcome. The Mod-MPI and E/A ratio have the potential to be integrated into routine surveillance techniques of the growth-restricted fetus. © 2014 John Wiley & Sons, Ltd.

Cardiac abnormalities in pulmonary oedema associated with hypertensive crises in pregnancy.

OBJECTIVE: To describe the cardiac abnormalities by two-dimensional and Doppler echocardiography (echo-Doppler) in hypertensive crises in pregnancy (HCP) complicated by pulmonary oedema and identify pathogenic factors. DESIGN: A prospective observational study. SETTING: King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: Sixteen patients with HCP complicated by pulmonary oedema over a six-month period. Two control groups, 55 patients with HCP alone and 16 with normotensive pregnancies, were also studied. RESULTS: Echocardiography diagnosed impaired left ventricular systolic function in 4 of 16 (25%) patients with HCP and pulmonary oedema. In the remaining 12 patients with preserved systolic function, left ventricular diastolic filling abnormalities were demonstrated in a significant proportion compared to control hypertensive and normotensive groups. Fifteen of 16 (94%) study patients presented with pulmonary oedema antepartum; in seven of these patients, the use of dexamethasone to enhance fetal lung maturity appeared to be a contributing factor in precipitating pulmonary oedema. CONCLUSION: This study demonstrates the value of echo-Doppler to diagnose structural and functional cardiac abnormalities in HCP complicated by pulmonary oedema. The potential role of left ventricular diastolic filling abnormalities in the pathogenesis of pulmonary oedema complicating HCP is discussed.

Malignant ventricular arrhythmias in eclampsia: a comparison of labetalol with dihydralazine.

OBJECTIVE: Our aim was to assess the impact of beta-adrenergic blockade during the peripartum period on the previously observed high incidence of ventricular arrhythmias in eclamptic parturients. STUDY DESIGN: An open, randomized comparison of intravenous labetalol versus dihydralazine was conducted in 40 eclamptic subjects in the peripartum period. Cardiac rhythm was assessed by blinded analysis of a 24-hour Holter record by means of the Lown classification of arrhythmias. RESULTS: There was a significantly higher incidence of serious ventricular arrhythmias in patients receiving dihydralazine (81%) than in those receiving labetalol (17%, p < 0.0001). Patients receiving labetalol showed a significant decrease in mean heart rate (p < 0.0001), whereas patients receiving dihydralazine showed a significant increase (p < 0.0001). CONCLUSION: The introduction of beta-adrenergic blockade into peripartum hypertensive management of eclampsia significantly reduced the incidence of dangerous ventricular arrhythmias. Myocardial oxygen supply/demand ratio may be improved by beta-blockade.

Continuous electrocardiographic monitoring in hypertensive crises in pregnancy.

Twenty-four patients first seen with hypertensive crises during pregnancy were studied by continuous electrocardiographic monitoring for a period of 24 hours to detect the presence of serious ventricular arrhythmias. Three patients were excluded from analysis because of low serum potassium levels. Thirteen of the remaining 21 patients had ventricular tachycardia on subsequent analysis of the electrocardiogram. These arrhythmias subsided after induction of anesthesia when blood pressure control was optimal. This finding may be implicated in the pathogenesis of pulmonary edema and sudden death in these patients.